Significant progress has been made in the development of a live attenuated subgroup A RSV vaccine and in understanding the genetic basis of attenuation of the biologically-derived, live-attenuated virus vaccine candidates. The complete nucleotide sequence of six live attenuated virus vaccine candidates has been determined. A menu of attenuating mutations has been assembled from this sequence analysis. This menu of attenuating mutations include: 1) the set of five mutations that are present in cpRSV; 2) four amino acid substitutions in the L gene each of which specifies the ts phenotype, specifically the single mutations present in the cold-passaged, temperature-sensitive (cpts) 530, 1009, 248 and 1030 mutants; and 3) a nucleotide substitution in the M2 gene start sequence that specifies the ts phenotype. These mutations are being introduced individually and in combinations into infectious RSV via cDNA intermediates, and the ts and attenuation (att) phenotypes of the recombinant viruses are being evaluated. Since the cpts248/404 candidate vaccine appears to be very promising in clinical trials but might need to be slightly further attenuated, emphasis is being placed on the reconstruction of this virus in cDNA form and the generation of cpts248/404 derivatives that contain one or two additional attenuating mutations. The RSV subgroup B cp52 candidate vaccine was found to be overattenuated in humans and sustained point mutations and a large deletion. The RSV subgroup B cp23 candidate vaccine which is attenuated in rodents will be administered to humans this year.